Conventional methods of dispersing a high potency, low dose drug into a physiologically inert material that is subsequently processed into a solid oral dosage form have involved preparing a premix or granulation in which a portion of one or more of the physiologically inert materials is first combined with the physiologically active compound using a low shear mixing device, such as a twinshell blender, a double cone blender, or a drum roll mixer. The premix or granulation is then passed through a mill, such as a Fitzpatrick® Comminutor, to enhance homogeneity of the mixture. The milled material can then be blended with other materials to form a final product mixture that is compressed into a tablet, filled into a capsule, or otherwise incorporated into a solid oral dosage form.
A problem with conventional techniques of dispersing a high potency, low dose drug into physiologically inert materials is that certain pharmaceutically active low dose drugs, such as loperamide hydrochloride, have a high affinity for adhering to surfaces of process containers and equipment. As a result, while an acceptably uniform or homogeneous distribution of the drug in the inert materials can be achieved using conventional methods, there can be a loss of potency in the final product due to adherence of the drug to process equipment surfaces. Further, loss of the active compound on process equipment surfaces represents a waste of the active compound, and ultimately a higher production cost.